The ultimate goal of this work is to understand how tissue interactions control differentiated cell behavior. These interactions are mediated by cell surface receptors. On epithelial cells, these receptors interact with the; extracellular matrix (ECM), as well as with adjacent cell surfaces, to provide anchorage and establish the high degree of polarity that characterizes differentiated epithelial cells. The ligands for these receptors are topically large and multivalent, forming an insoluble scaffolding that immobilizes the receptor and is likely to convey information to the cell. The information may be interpreted via cytoskeletal organization leading to specific cell shape. In addition failure to anchor the receptor may allow its loss from the surface by internalization, conveying a signal to the interior of the cell. A cell surface proteoglycan (syndecan) of epithelial cells binds a variety of matrix ligands, is anchored to the cytoskeleton and exhibits variable life-times at the cell surface. In addition, its ability to recognize its ligands may be modified by alterations in its structure during synthesis. This proposal is to study the mechanisms that promote the anchorage of syndecan to the ECM and cytoskeleton, understand why its structure changes with cell behavior and identify the reason for its sorting when removed from the cell surface. An understanding of the molecules and mechanisms that allow external interactions of cells to be recognized, translated, and transmitted across the plasma membrane to the cytoplasm is required to develop rational means of preventing the abnormalities in organ morphogenesis and cell behavior that lead to diseases and birth defects.